Toxicity and morbility after isolated lower limb perfusion in 242 chemo-hyperthermal treatments for cutaneous melanoma: The experience of the Tuscan Reference Centre

<p>Abstract</p> <p>Background</p> <p>The aim of this retrospective study was to assess the results concerning the regional and systemic toxicity and complications in 242 chemo-hyperthermal treatments (HILPs) for lower limb melanoma.</p> <p>Patients and methods</p> <p>60 HILPs (G-A) were performed with mild HT plus L-PAM (10 mg/lt) ± D-actimomycin; 74 HILPs (G-B) with true HT (40–41.8°C) plus L-PAM (10 mg/lt) ± D-act; 108 HILPs (G-C) with true HT plus L-PAM (10 mg/lt) ± D-act plus L-PAM (5 mg/lt) additional bolus.</p> <p>Results</p> <p>Limb toxicity was very low in G-A and in G-B; increasing toxicity (grade III = 37%) in G-C; no grade IV statistical difference was registered in all three groups, with percentage values among 1.6% and 2.7%. Systemic toxicity showed itself only in the haemopoietic parameters. No differences were registered in G-B vs G-A group. In G-C vs G-B a significative increase of systemic toxicity was seen in grade 3 (p < 0.05). Postoperative complications were acceptable. Local and systemic side-effects were transient; no permanent neurological limb deficit was registered. The postoperative mortality was recorded in 3/182 HILPs (1.6%) of the G-B and G-C groups.</p> <p>Conclusion</p> <p>These data suggested that the technical implementations reduced the occurrence and the severity of the side effects and complications. The essential requirement for HILP is the quality assurance of the procedures. Although higher regional and systemic toxicity were observed in the G-C group caused by L-PAM additional bolus, the safeness of the procedures under the true hyperthermal regimen and the time increase of the high L-PAM concentration have assured the treatment reliability along with the increased clinical efficacy expectations of the treatments.</p

Association of Noncontrast Computed Tomography and Perfusion Modalities With Outcomes in Patients Undergoing Late-Window Stroke Thrombectomy

Importance: There is substantial controversy with regards to the adequacy and use of noncontrast head computed tomography (NCCT) for late-window acute ischemic stroke in selecting candidates for mechanical thrombectomy. Objective: To assess clinical outcomes of patients with acute ischemic stroke presenting in the late window who underwent mechanical thrombectomy stratified by NCCT admission in comparison with selection by CT perfusion (CTP) and diffusion-weighted imaging (DWI). Design, setting, and participants: In this multicenter retrospective cohort study, prospectively maintained Stroke Thrombectomy and Aneurysm (STAR) database was used by selecting patients within the late window of acute ischemic stroke and emergent large vessel occlusion from 2013 to 2021. Patients were selected by NCCT, CTP, and DWI. Admission Alberta Stroke Program Early CT Score (ASPECTS) as well as confounding variables were adjusted. Follow-up duration was 90 days. Data were analyzed from November 2021 to March 2022. Exposures: Selection by NCCT, CTP, or DWI. Main outcomes and measures: Primary outcome was functional independence (modified Rankin scale 0-2) at 90 days. Results: Among 3356 patients, 733 underwent late-window mechanical thrombectomy. The median (IQR) age was 69 (58-80) years, 392 (53.5%) were female, and 449 (65.1%) were White. A total of 419 were selected with NCCT, 280 with CTP, and 34 with DWI. Mean (IQR) admission ASPECTS were comparable among groups (NCCT, 8 [7-9]; CTP, 8 [7-9]; DWI 8, [7-9]; P = .37). There was no difference in the 90-day rate of functional independence (aOR, 1.00; 95% CI, 0.59-1.71; P = .99) after adjusting for confounders. Symptomatic intracerebral hemorrhage (NCCT, 34 [8.6%]; CTP, 37 [13.5%]; DWI, 3 [9.1%]; P = .12) and mortality (NCCT, 78 [27.4%]; CTP, 38 [21.1%]; DWI, 7 [29.2%]; P = .29) were similar among groups. Conclusions and relevance: In this cohort study, comparable outcomes were observed in patients in the late window irrespective of neuroimaging selection criteria. Admission NCCT scan may triage emergent large vessel occlusion in the late window

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Effect of Workflow Improvements in Endovascular Stroke Treatment

Background and Purpose—Rapid initiation of endovascular stroke treatment is associated with better clinical outcome. The effect of specific improvements is not well known. We performed a systematic review and meta-analysis on the effectiveness of specific workflow improvements on time to treatment and outcome. Methods—A random-effects meta-analysis was used to evaluate the difference in mean time to treatment between intervention group and control group. Secondary outcomes included good functional outcome at 90 days (modified Rankin Scale score 0–2). Results—Fifty-one studies (3 randomized controlled trials, 13 prepost intervention studies, and 35 observational studies) with in total 8467 patients were included. Most frequently reported workflow intervention types concerned anesthetic management (n=26), in-hospital patient transfer management (n=14), and prehospital management (n=11). Patients in the intervention group had shorter time to treatment intervals (weighted mean difference, 26 minutes; 95% CI, 19–33; P<0.001) compared with controls. Subgroup meta-analysis of intervention types also showed a shorter time to treatment in the intervention group: a mean difference of 12 minutes (95% CI, 6–17; P<0.001) for anesthetic management, 37 minutes (95% CI, 22–52; P<0.001) for prehospital management, 41 minutes (95% CI, 27–54; P<0.001) for in-hospital patient transfer management, 47 minutes (95% CI, 28–67; P<0.001) for teamwork, and 64 minutes (95% CI, 24–104; P=0.002) for feedback. The mean difference in time to treatment of studies with multiple interventions implemented simultaneously was 50 minutes (95% CI, 31–69; P<0.001) in favor of the intervention group. Patients in the intervention group had increased likelihood of favorable outcome (risk ratio [RR], 1.39; 95% CI, 1.15–1.66; P<0.001). Conclusions—Interventions in the workflow of endovascular stroke treatment lead to a significant reduction in time to treatment and results in an increased likelihood of favorable outcome. Acute stroke care should be reorganized by making use of the examples of workflow interventions described in this review to ensure the best medical care for stroke patients